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Neo ALTTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) Study (Neo ALTTO)

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ClinicalTrials.gov Identifier: NCT00553358
Recruitment Status : Active, not recruiting
First Posted : November 5, 2007
Results First Posted : October 13, 2011
Last Update Posted : October 10, 2019
Sponsor:
Collaborators:
Breast International Group
SOLTI Breast Cancer Research Group
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neoplasms, Breast
Interventions Drug: Lapatinib
Biological: Trastuzumab
Drug: Paclitaxel
Enrollment 455
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenously (IV) for an additional 12 weeks Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Period Title: Overall Study
Started 154 149 152
Completed 101 137 92
Not Completed 53 12 60
Reason Not Completed
Adverse Event             29             2             32
Lost to Follow-up             0             0             1
Protocol Violation             0             1             1
Withdrawal by Subject             5             0             1
Recurrence of Disease             3             4             1
Participant Withdrawal from Drug             0             0             3
Missing             1             1             1
Other: Reason Not Specified             15             4             20
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg Total
Hide Arm/Group Description Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenously (IV) for an additional 12 weeks Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks Total of all reporting groups
Overall Number of Baseline Participants 154 149 152 455
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 154 participants 149 participants 152 participants 455 participants
50.0
(28 to 79)
49.0
(23 to 77)
50.0
(25 to 80)
50.0
(23 to 80)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 154 participants 149 participants 152 participants 455 participants
Female
154
 100.0%
149
 100.0%
152
 100.0%
455
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 154 participants 149 participants 152 participants 455 participants
American Indian or Alaska Native 13 14 15 42
Asian - Central/South 7 5 5 17
Asian - East 30 28 31 89
Asian - South East 0 0 2 2
Black or African American/African Heritage 0 4 4 8
White - Arabic/North African Heritage 6 5 3 14
White - Caucasian European Heritage 97 93 92 282
Missing 1 0 0 1
Number of participants with tumor cells of the indicated histologic grade   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 154 participants 149 participants 152 participants 455 participants
Well differentiated 2 5 5 12
Moderately differentiated 56 53 63 172
Poorly differentiated 73 68 64 205
Differentiation cannot be assessed 22 23 20 65
Missing 1 0 0 1
[1]
Measure Description: Histologic grade, also called differentiation, refers to how much the tumor cells resemble normal cells of the same tissue type.
Number of participants with lymph nodes (LNs) of the indicated clinical N stage   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 154 participants 149 participants 152 participants 455 participants
N0 34 41 48 123
N1 95 85 80 260
N2 (including N2a and N2b) 19 13 15 47
N3 (including N3a, N3b, and N3c) 6 7 6 19
Nx 0 3 3 6
[1]
Measure Description: Clinical N stage is an evaluation/staging of LN status through physical examination. N0, no regional LN metastasis; N1, metastasis to movable ipsilateral axillary LNs (IALNs); N2a, metastasis in IALNs fixed to one another (matted) or the other structures; N2b, metastasis only in clinically apparent ipsilateral internal mammary nodes and in the absence of clinically evident axillary LN metastasis; N3a, metastasis in ipsilateral infraclavicular LNs; N3b, metastasis in ipsilateral internal mammary LNs fixed and axillary LN; N3c, metastasis in ipsilateral subclavicar LNs; Nx, not assessed.
Number of participants with the indicated IHC results   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 154 participants 149 participants 152 participants 455 participants
Not applicable 60 53 61 174
Equivocal: Score of 2+ 9 5 8 22
Positive: Score of 3+ 81 89 76 246
Negative: Score of 0-1+ 0 1 3 4
Non interpretable 4 1 4 9
[1]
Measure Description: An Immunohistochemistry (IHC) test gives a score of 0 to 3+, which indicates the amount of Human Epidermal Growth Factor (HER2) receptor proteins on the cancer cells in the sample tissue. A positive score (3+) indicates that HER2 receptor protein is present, a negative score (0-1+) indicates that no HER2 receptor protein is present, and an equivocal score (2+) indicates uncertainty and a result that is open for interpretation. Equivocal results require additional testing. “Not applicable” refers to the number of participants who did not have IHC testing done.
Number of participants with the indicated FISH results   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 154 participants 149 participants 152 participants 455 participants
Not applicable 38 42 41 121
Amplified 115 105 109 329
Not amplified 1 2 1 4
Not interpretable 0 0 1 1
[1]
Measure Description: The Fluorescent In Situ Hybridization (FISH) assay was used to determine the overexpression and/or amplification of HER2 in the invasive component of the primary tumor. Amplified indicates that the cell is overexpressing copies of the HER2 gene. Not amplified indicates that there is no overexpression of copies of the HER2 gene. “Not applicable” refers to the number of participants who did not have the FISH assay performed.
1.Primary Outcome
Title Number of Participants With Pathological Complete Response (pCR) at the Time of Surgery
Hide Description Pathological complete response is defined as no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. Surgical breast and axillary node resection specimens were evaluated for pathologic tumor response according to National Surgical Adjuvant Breast and Bowel Project (NSABP) guidelines, which do not take into account the histological nodal status.
Time Frame Weeks 20 to 22
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all participants randomized to treatment, except for those who withdrew their consent to use any of their data (permitted by law in certain countries) prior to receiving any study medication
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 154 149 152
Measure Type: Number
Unit of Measure: participants
38 44 78
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lapatinib 1500 mg, Trastuzumab 2 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3416
Comments [Not Specified]
Method Binomial
Comments Binomial p-value for Trastuzumab 2 mg/kg versus Lapatinib 1500 mg
Method of Estimation Estimation Parameter Percentage of participants with pCR
Estimated Value -4.85
Confidence Interval (2-Sided) 97.5%
-17.6 to 8.16
Estimation Comments Estimation Comments: Estimated value is the difference in the percentage of participants with pCR: Arm1 (Lapatinib 1500 mg) minus Arm2 (Trastuzumab 2 mg/kg)
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Trastuzumab 2 mg/kg, Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Binomial
Comments Binomial p-value for Trastuzumab 2 mg/kg versus Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Method of Estimation Estimation Parameter Percentage of participants with pCR
Estimated Value 21.79
Confidence Interval (2-Sided) 97.5%
9.08 to 34.23
Estimation Comments Estimation Comments: Estimated value is the difference in the percentage of participants with pCR: Arm3 (Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg) minus Arm2 (Trastuzumab 2 mg/kg)
2.Secondary Outcome
Title Number of Participants With Overall Response at Week 6
Hide Description The number of participants with overall response (complete response and/or partial response) was evaluated using World Health Organization (WHO) criteria by clinical examination and by mammography and breast echography with bi-dimensional measurements at Week 6. As per WHO criteria: complete response is defined as the disappearance of all lesions; partial response is defined as a greater than 50% decrease in the sum of products of the greatest length and width of the largest lesion; progressive disease is defined as a greater than 25% increase in the sum of products of all measurable lesions.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 154 149 152
Measure Type: Number
Unit of Measure: participants
Overall Response 81 45 102
No Change 57 81 33
Progressive Disease 5 11 2
Not Evaluated 7 9 12
Missing Data 4 3 3
3.Secondary Outcome
Title Number of Participants With Overall Response at the Time of Surgery
Hide Description The number of participants with overall response (complete response and/or partial response) was evaluated using WHO criteria by clinical examination and mammography and breast echography with bi-dimensional measurements at the time of surgery (Weeks 20 to 22). As per WHO criteria: complete response is defined as the disappearance of all lesions; partial response is defined as a greater than 50% decrease in the sum of products of the greatest length and width of the largest lesion; progressive disease is defined as a greater than 25% increase in the sum of products of all measurable lesions.
Time Frame Time of surgery (Weeks 20 to 22)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 154 149 152
Measure Type: Number
Unit of Measure: participants
Overall Response 114 105 122
No Change 8 16 7
Progressive Disease 0 2 1
Not Evaluated 19 20 14
Missing Data 13 6 8
4.Secondary Outcome
Title Number of Participants With Negative Lymph Nodes at the Time of Surgery
Hide Description Participants were assessed for node-negative lymph nodes at the time of surgery. As per the pathological TNM (Tumor, Node, Metastases) classification (pTNM) of malignant tumors: pN, absence or presence and extent of regional lymph node metastasis. Node-negative (pN0) participants had no regional lymph node metastasis. Although not assessed in this measure, pT is the extent of primary tumor, and pM is the absence or presence of distant metastasis.
Time Frame Time of surgery (Weeks 20 to 22)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Participants with a lymph node status of pNX (i.e., regional lymph nodes cannot be assessed) were omitted from the analysis of node-negative participants.
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 130 134 128
Measure Type: Number
Unit of Measure: participants
64 78 91
5.Secondary Outcome
Title Number of Participants With Actual Indicated Surgery
Hide Description Participants were assessed for the type of surgery they underwent for breast cancer. Non-conservative surgery is defined as a radical or modified radical mastectomy. Conservative surgery is comprised of a lumpectomy, a quadrantectomy/segmentectomy, or a partial mastectomy. Participants who were not assessed as being candidates for non-conservative or conservative surgery were classified as non-operable.
Time Frame At surgery (Weeks 20 to 22)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 154 149 152
Measure Type: Number
Unit of Measure: participants
Conservative 66 58 63
Non-conservative 77 85 80
Non-operable 11 6 9
6.Secondary Outcome
Title Estimate of Treatment Contrast for Change From Baseline in Tumor Size at Week 6 and at Surgery
Hide Description Estimate of treatment contrast is defined as the estimate of the difference between treatment groups in the change from baseline in tumor size. Change from baseline in tumor size was defined as tumor size at Week 6/ surgery (Weeks 20 to 22) minus tumor size at baseline. The difference in treatment arms was estimated for Lapatinib 1500 mg versus Trastuzumab 2 mg/kg and for Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg versus Trastuzumab 2 mg/kg.
Time Frame Week 6 and surgery (Weeks 20 to 22)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 154 149 152
Mean (Standard Deviation)
Unit of Measure: millimeters
Week 6 -20.45  (18.43) -13.42  (16.44) -25.77  (19.91)
Surgery (Weeks 20 to 22) -41.01  (23.81) -35.47  (22.95) -43.59  (26.88)
7.Secondary Outcome
Title Number of Participants Starting Paclitaxel Before Completing 6 Weeks of Treatment With Either Lapatinib or Trastuzumab
Hide Description Participants with progressive disease at 4 week assessment that were permitted to commence treatment with paclitaxel.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Participants who did not start any treatment were excluded from analysis.
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 149 146 149
Measure Type: Number
Unit of Measure: participants
8 12 6
8.Secondary Outcome
Title Overall Survival
Hide Description Overall survival was defined as the period from surgery until death (from any cause). Data will be reported when they are mature and available; OS is assessed annually for up to 10 years after the randomization of the last participant into the study.
Time Frame Following surgery, every 12 months until Year 10
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Disease-free Survival (DFS)
Hide Description DFS was defined as the time from surgery to the first date of breast cancer relapse, second primary tumor (including contralateral breast cancer), or death without documented prior relapse. Data will be reported when they are mature and available, likely when a median of 3 years follow up has been reached.
Time Frame Following surgery, every 12 months until Year 10
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Number of Participants With Metabolic Response of Complete Response (mCR), Partial Response (mPR), or Stable Disease (mSD) as Determined by Positron Emission Tomography/Computed Tomography (PET/CT)
Hide Description European Organisation for Research and Treatment of Cancer recommendations were used to define metabolic response. mCR, complete metabolic response: complete resolution of fludeoxyglucose uptake within tumor, indistinguishable from surrounding normal tissue. mPR, partial metabolic response: reduction of more than 25% of maximum tumor standard uptake value (SUV). mSD, stable metabolic disease: increase of <25% in tumor SUV or decrease of >20% in tumor SUV. mPD, progressive metabolic disease: increase of >25% in tumor SUV or >20% in the extent (longest dimension) or appearance of new metastases.
Time Frame Baseline, Week 2, and Week 6
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Number of Participants With the Indicated Biomarker Expression
Hide Description Biomarker levels (Ki67, p27, Cyclin-D1, ErbB1, ErbB2, ErbB3, pErbB1, pErbB2, Akt and pAkt, S6 and pS6, MAPK and pMAPK, c-myc, IGFR1, p95HER2, PTEN, ER (alpha, beta), PgR,CD34, terminal deoxynucleotidyl transferase biotin-dUTP nick and labelling technique [TUNEL] and topoisomerase II) were assessed in participants. Blood and tumor tissue samples were collected at Baseline and at Weeks 2 and 20-22; however, data for this outcome measure cannot be presented at this time as they have yet to be evaluated and reviewed.
Time Frame Baseline, Week 2, and at surgery (Weeks 20 to 22)
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Number of Circulating Tumor Cells (CTC) in the Bloodstream
Hide Description Circulating tumor cells (CTCs) are cells that have detached from a primary tumor and circulate in the bloodstream. In the adjuvant phase, after surgery all participants received 3 courses of adjuvant 5-fluorouracil, epirubicin and cyclophosphamide, followed by lapatinib 1500 mg or trastuzumab 2 mg/kg or lapatinib 1000/750 mg plus trastuzumab 2 mg/kg given prior to surgery in the neoadjuvant setting for an additional 34 weeks. Data for this outcome measure cannot be presented at this time as they have yet to be evaluated and reviewed.
Time Frame Baseline, Week 2 of neo-adjuvant phase (Weeks 1-34), at surgery (Weeks 20 to 22), Week 10 of adjuvant phase, 6 months after completion of adjuvant treatment, and at recurrence
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description Only events, assessments, and treatments with a start date on or before the end date of the neoadjuvant phase have been summarized. One non-serious event was reported as an uncoded event. A non-serious event of dental care was actually coded to "Surgical and medical procedures."
 
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
All-Cause Mortality
Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   40/154 (25.97%)   9/149 (6.04%)   35/152 (23.03%) 
Blood and lymphatic system disorders       
Neutropenia  1  2/154 (1.30%)  2/149 (1.34%)  2/152 (1.32%) 
Leukopenia  1  0/154 (0.00%)  0/149 (0.00%)  1/152 (0.66%) 
Pancytopenia  1  0/154 (0.00%)  0/149 (0.00%)  1/152 (0.66%) 
Anemia  1  1/154 (0.65%)  0/149 (0.00%)  0/152 (0.00%) 
Febrile neutropenia  1  1/154 (0.65%)  0/149 (0.00%)  0/152 (0.00%) 
Cardiac disorders       
Cardio-respiratory arrest  1  0/154 (0.00%)  0/149 (0.00%)  1/152 (0.66%) 
Cardiac failure congestive  1  0/154 (0.00%)  0/149 (0.00%)  1/152 (0.66%) 
Gastrointestinal disorders       
Diarrhea  1  9/154 (5.84%)  0/149 (0.00%)  8/152 (5.26%) 
Vomiting  1  0/154 (0.00%)  0/149 (0.00%)  3/152 (1.97%) 
Nausea  1  0/154 (0.00%)  0/149 (0.00%)  2/152 (1.32%) 
Duodenitis  1  0/154 (0.00%)  0/149 (0.00%)  1/152 (0.66%) 
Enteritis  1  0/154 (0.00%)  0/149 (0.00%)  1/152 (0.66%) 
Gastritis erosive  1  0/154 (0.00%)  0/149 (0.00%)  1/152 (0.66%) 
Gastrointestinal hemorrhage  1  0/154 (0.00%)  0/149 (0.00%)  1/152 (0.66%) 
General disorders       
Pyrexia  1  2/154 (1.30%)  1/149 (0.67%)  3/152 (1.97%) 
Asthenia  1  0/154 (0.00%)  0/149 (0.00%)  1/152 (0.66%) 
Chest pain  1  1/154 (0.65%)  0/149 (0.00%)  0/152 (0.00%) 
General physical health deterioration  1  1/154 (0.65%)  0/149 (0.00%)  0/152 (0.00%) 
Infusion related reaction  1  0/154 (0.00%)  1/149 (0.67%)  0/152 (0.00%) 
Hepatobiliary disorders       
Hypertransaminasemia  1  20/154 (12.99%)  2/149 (1.34%)  13/152 (8.55%) 
Hyperbilirubinemia  1  4/154 (2.60%)  0/149 (0.00%)  3/152 (1.97%) 
Pancreatitis  1  1/154 (0.65%)  0/149 (0.00%)  0/152 (0.00%) 
Infections and infestations       
Device related infection  1  0/154 (0.00%)  0/149 (0.00%)  2/152 (1.32%) 
Device related sepsis  1  1/154 (0.65%)  0/149 (0.00%)  0/152 (0.00%) 
Pharyngitis  1  0/154 (0.00%)  0/149 (0.00%)  1/152 (0.66%) 
Pneumonia  1  0/154 (0.00%)  0/149 (0.00%)  1/152 (0.66%) 
Bacterial sepsis  1  1/154 (0.65%)  0/149 (0.00%)  0/152 (0.00%) 
Hepatitis B  1  1/154 (0.65%)  0/149 (0.00%)  0/152 (0.00%) 
Herpes zoster  1  1/154 (0.65%)  1/149 (0.67%)  0/152 (0.00%) 
Herpes simplex  1  1/154 (0.65%)  0/149 (0.00%)  0/152 (0.00%) 
Urinary tract infection  1  2/154 (1.30%)  0/149 (0.00%)  0/152 (0.00%) 
Injury, poisoning and procedural complications       
Transfusion reaction  1  0/154 (0.00%)  0/149 (0.00%)  1/152 (0.66%) 
Poisoning  1  1/154 (0.65%)  0/149 (0.00%)  0/152 (0.00%) 
Investigations       
Gamma-glutamyltransferase increased  1  1/154 (0.65%)  0/149 (0.00%)  1/152 (0.66%) 
Metabolism and nutrition disorders       
Hyperphosphatasemia  1  0/154 (0.00%)  0/149 (0.00%)  1/152 (0.66%) 
Dehydration  1  2/154 (1.30%)  0/149 (0.00%)  0/152 (0.00%) 
Diabetes mellitus  1  0/154 (0.00%)  1/149 (0.67%)  0/152 (0.00%) 
Hypokalemia  1  1/154 (0.65%)  0/149 (0.00%)  0/152 (0.00%) 
Hypoglycemia  1  0/154 (0.00%)  0/149 (0.00%)  1/152 (0.66%) 
Nervous system disorders       
Headache  1  0/154 (0.00%)  1/149 (0.67%)  0/152 (0.00%) 
Neuropathy peripheral  1  1/154 (0.65%)  0/149 (0.00%)  0/152 (0.00%) 
Renal and urinary disorders       
Renal failure acute  1  1/154 (0.65%)  0/149 (0.00%)  2/152 (1.32%) 
Nephrectasia  1  1/154 (0.65%)  0/149 (0.00%)  0/152 (0.00%) 
Nephrolithiasis  1  1/154 (0.65%)  0/149 (0.00%)  0/152 (0.00%) 
Reproductive system and breast disorders       
Vulvovaginal pruritus  1  1/154 (0.65%)  0/149 (0.00%)  0/152 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Interstitial lung disease  1  0/154 (0.00%)  0/149 (0.00%)  2/152 (1.32%) 
Pneumonitis  1  0/154 (0.00%)  0/149 (0.00%)  1/152 (0.66%) 
Pneumothorax  1  1/154 (0.65%)  0/149 (0.00%)  0/152 (0.00%) 
Skin and subcutaneous tissue disorders       
Acne  1  0/154 (0.00%)  0/149 (0.00%)  1/152 (0.66%) 
Vascular disorders       
Jugular vein thrombosis  1  0/154 (0.00%)  1/149 (0.67%)  0/152 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   143/154 (92.86%)   123/149 (82.55%)   138/152 (90.79%) 
Blood and lymphatic system disorders       
Anaemia  1  24/154 (15.58%)  19/149 (12.75%)  34/152 (22.37%) 
Neutropenia  1  34/154 (22.08%)  10/149 (6.71%)  25/152 (16.45%) 
Leukopenia  1  10/154 (6.49%)  5/149 (3.36%)  9/152 (5.92%) 
Gastrointestinal disorders       
Diarrhoea  1  118/154 (76.62%)  39/149 (26.17%)  117/152 (76.97%) 
Nausea  1  56/154 (36.36%)  32/149 (21.48%)  42/152 (27.63%) 
Vomiting  1  29/154 (18.83%)  12/149 (8.05%)  29/152 (19.08%) 
Abdominal pain  1  25/154 (16.23%)  8/149 (5.37%)  18/152 (11.84%) 
Stomatitis  1  15/154 (9.74%)  12/149 (8.05%)  22/152 (14.47%) 
Abdominal pain upper  1  19/154 (12.34%)  11/149 (7.38%)  15/152 (9.87%) 
Dyspepsia  1  20/154 (12.99%)  7/149 (4.70%)  12/152 (7.89%) 
Constipation  1  9/154 (5.84%)  10/149 (6.71%)  5/152 (3.29%) 
Abdominal distension  1  8/154 (5.19%)  5/149 (3.36%)  9/152 (5.92%) 
Haemorrhoids  1  9/154 (5.84%)  4/149 (2.68%)  6/152 (3.95%) 
Mouth ulceration  1  0/154 (0.00%)  1/149 (0.67%)  8/152 (5.26%) 
General disorders       
Asthenia  1  45/154 (29.22%)  27/149 (18.12%)  31/152 (20.39%) 
Fatigue  1  33/154 (21.43%)  26/149 (17.45%)  36/152 (23.68%) 
Mucosal inflammation  1  29/154 (18.83%)  15/149 (10.07%)  24/152 (15.79%) 
Pyrexia  1  13/154 (8.44%)  17/149 (11.41%)  23/152 (15.13%) 
Chills  1  1/154 (0.65%)  4/149 (2.68%)  9/152 (5.92%) 
Hepatobiliary disorders       
Hypertransaminasaemia  1  46/154 (29.87%)  32/149 (21.48%)  46/152 (30.26%) 
Hyperbilirubinaemia  1  21/154 (13.64%)  4/149 (2.68%)  19/152 (12.50%) 
Infections and infestations       
Nasopharyngitis  1  11/154 (7.14%)  7/149 (4.70%)  8/152 (5.26%) 
Urinary tract infection  1  11/154 (7.14%)  4/149 (2.68%)  5/152 (3.29%) 
Paronychia  1  2/154 (1.30%)  0/149 (0.00%)  10/152 (6.58%) 
Investigations       
Weight decreased  1  9/154 (5.84%)  0/149 (0.00%)  6/152 (3.95%) 
Metabolism and nutrition disorders       
Decreased appetite  1  34/154 (22.08%)  10/149 (6.71%)  30/152 (19.74%) 
Hyperphosphatasaemia  1  16/154 (10.39%)  8/149 (5.37%)  16/152 (10.53%) 
Musculoskeletal and connective tissue disorders       
Myalgia  1  27/154 (17.53%)  25/149 (16.78%)  24/152 (15.79%) 
Arthralgia  1  13/154 (8.44%)  13/149 (8.72%)  9/152 (5.92%) 
Musculoskeletal pain  1  11/154 (7.14%)  5/149 (3.36%)  4/152 (2.63%) 
Back pain  1  4/154 (2.60%)  6/149 (4.03%)  9/152 (5.92%) 
Nervous system disorders       
Headache  1  14/154 (9.09%)  22/149 (14.77%)  16/152 (10.53%) 
Neuropathy peripheral  1  15/154 (9.74%)  17/149 (11.41%)  14/152 (9.21%) 
Paraesthesia  1  9/154 (5.84%)  14/149 (9.40%)  19/152 (12.50%) 
Peripheral sensory neuropathy  1  14/154 (9.09%)  12/149 (8.05%)  9/152 (5.92%) 
Dizziness  1  11/154 (7.14%)  11/149 (7.38%)  7/152 (4.61%) 
Hypoaesthesia  1  6/154 (3.90%)  9/149 (6.04%)  9/152 (5.92%) 
Dysgeusia  1  11/154 (7.14%)  1/149 (0.67%)  11/152 (7.24%) 
Psychiatric disorders       
Insomnia  1  15/154 (9.74%)  16/149 (10.74%)  17/152 (11.18%) 
Renal and urinary disorders       
Dysuria  1  3/154 (1.95%)  1/149 (0.67%)  9/152 (5.92%) 
Reproductive system and breast disorders       
Breast pain  1  3/154 (1.95%)  9/149 (6.04%)  2/152 (1.32%) 
Respiratory, thoracic and mediastinal disorders       
Epistaxis  1  28/154 (18.18%)  21/149 (14.09%)  29/152 (19.08%) 
Cough  1  12/154 (7.79%)  17/149 (11.41%)  14/152 (9.21%) 
Oropharyngeal pain  1  15/154 (9.74%)  8/149 (5.37%)  8/152 (5.26%) 
Dyspnoea  1  9/154 (5.84%)  6/149 (4.03%)  9/152 (5.92%) 
Rhinorrhoea  1  4/154 (2.60%)  8/149 (5.37%)  9/152 (5.92%) 
Skin and subcutaneous tissue disorders       
Alopecia  1  75/154 (48.70%)  75/149 (50.34%)  79/152 (51.97%) 
Rash  1  59/154 (38.31%)  19/149 (12.75%)  57/152 (37.50%) 
Nail disorder  1  15/154 (9.74%)  8/149 (5.37%)  24/152 (15.79%) 
Dry skin  1  21/154 (13.64%)  4/149 (2.68%)  19/152 (12.50%) 
Acne  1  20/154 (12.99%)  3/149 (2.01%)  17/152 (11.18%) 
Pruritus  1  19/154 (12.34%)  4/149 (2.68%)  17/152 (11.18%) 
Dermatitis acneiform  1  10/154 (6.49%)  4/149 (2.68%)  11/152 (7.24%) 
Erythema  1  10/154 (6.49%)  4/149 (2.68%)  9/152 (5.92%) 
Skin fissures  1  2/154 (1.30%)  4/149 (2.68%)  10/152 (6.58%) 
Palmar-Plantar erythrodysaesthesia syndrome  1  5/154 (3.25%)  1/149 (0.67%)  8/152 (5.26%) 
Vascular disorders       
Hot flush  1  7/154 (4.55%)  4/149 (2.68%)  9/152 (5.92%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Disclosure Office
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Publications:
Baselga J, Piccart M, Gelber R, di CosimoS, Viale G, Koehler M, Rojo F. Neo-ALTTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) study [BIG 1-06 /solti/EGF106903]: a phase III translational study for HER2-overexpressing early breast cancer. [Lancet]. 2012;S140-6736(11):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00553358     History of Changes
Other Study ID Numbers: EGF106903
First Submitted: November 1, 2007
First Posted: November 5, 2007
Results First Submitted: May 26, 2011
Results First Posted: October 13, 2011
Last Update Posted: October 10, 2019